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| 2. |
- Gustavsson, Anders, et al.
(författare)
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Disease progression and costs of care in Alzheimer's disease patients treated with donepezil: a longitudinal naturalistic cohort.
- 2012
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Ingår i: European Journal of Health Economics. - : Springer Science and Business Media LLC. - 1618-7601 .- 1618-7598. ; 13:5, s. 561-568
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: Improved data and methods are needed for modeling disease progression in Alzheimer's disease (AD) for economic evaluation of treatments. The aim is to estimate prediction models for long-term AD progression and subsequently economic outcomes. METHODS: Three-year follow-up data on 435 patients treated with the cholinesterase inhibitor donepezil in clinical practise were analyzed. Regression models were estimated for long-term prediction of decline in cognitive function (ADAS-cog) and activities in daily living (ADL) ability, risk of institutionalization and costs of care. RESULTS: The cognitive deterioration was estimated at between 1.6 and 4 ADAS-cog points per every 6 months, increasing with disease severity. Cognitive function was an important predictor of ADL-ability, which itself was the most important predictor of the risk of institutionalization and costs of care. Combining all models in a cross-validation process generated accurate predictions of costs of care at each 6 months follow-up. CONCLUSION: The proposed methods for representing AD progression and economic outcomes can be used in micro-simulation models for the economic evaluation of new treatments.
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- Minthon, Lennart, et al.
(författare)
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Long-term rivastigmine treatment in a routine clinical setting.
- 2009
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Ingår i: Acta Neurologica Scandinavica. - : Wiley Blackwell. - 0001-6314 .- 1600-0404. ; 119:3, s. 180-185
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of the study was to observe the effects of long-term rivastigmine treatment in patients with mild to moderate Alzheimer's disease (AD) in a routine clinical setting. METHODS: This was a prospective, open-label, observational, multicentre, non-randomized study. Outcome measures included the Mini Mental State Examination (MMSE), the Clinician's Interview-Based Impression of Change (CIBIC) and the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog). RESULTS: Of 217 patients initiated into rivastigmine treatment, 62% (n = 135) remained on treatment for 24 months. Most patients droped out due to nursing home placement or side effects. Eighty per cent and 67% of completers exhibited a symptomatic attenuation of cognitive decline (< or = 4-point deterioration) as assessed by using the MMSE and ADAS-cog respectively. Forty-four per cent showed an unchanged/improved CIBIC rating. CONCLUSIONS: Over 60% of patients remained on treatment for 2 years in this routine clinical setting. In patients who remained on treatment, rivastigmine appeared to stabilize their condition and prevented or delayed symptomatic decline.
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| 5. |
- Persson, Cecilia, et al.
(författare)
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Changes in cognitive domains during three years in patients with Alzheimer's disease treated with donepezil
- 2009
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Ingår i: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: The objective was to identify separate cognitive domains in the standard assessment tools (MMSE, ADAS-Cog) and analyze the process of decline within domains during three years in Alzheimer's disease (AD) patients with donepezil treatment. Method: AD patients (n = 421) were recruited from a clinical multi-centre study program in Sweden. Patients were assessed every six months during three years. All patients received donepezil starting directly after study entry. After dropouts, 158 patients remained for analyses over three years. Data for the other patients were analysed until they dropped out (4 groups based on length in study). Results: Factor analyses of all items suggested that there were three intercorrelated factors: a General, a Memory and a Spatial factor for which we constructed corresponding domains. Overall there was a cognitive improvement at six months followed by a linear drop over time for the three domains. Some group and domain differences were identified. Patients who remained longer in the study had better initial performance and a slower deterioration rate. The early dropouts showed no improvement at six months and many dropped out due to side effects. The other groups displayed a performance improvement at six months that was less pronounced in the Memory domain. Before dropping out, deterioration accelerated, particularly in the Spatial domain. Conclusion: The course of illness in the three domains was heterogeneous among the patients. We were not able to identify any clinically relevant correlates of this heterogeneity. As an aid we constructed three algorithms corresponding to the cognitive domains, which can be used to characterize patients initially, identify rapid decliners and follow the course of the disease.
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| 6. |
- Visser, Pieter Jelle, et al.
(författare)
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Prevalence and prognostic value of CSF markers of Alzheimer's disease pathology in patients with subjective cognitive impairment or mild cognitive impairment in the DESCRIPA study: a prospective cohort study.
- 2009
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Ingår i: Lancet neurology. - : The Lancet Publishing Group. - 1474-4422 .- 1474-4465. ; 8:7, s. 619-27
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Alzheimer's disease (AD) pathology is common in patients with amnestic mild cognitive impairment (aMCI) without dementia, but the prevalence of AD pathology in patients with subjective cognitive impairment (SCI) and non-amnestic mild cognitive impairment (naMCI) is unknown. AD is characterised by decreased CSF concentrations of Abeta(42) and increased concentrations of tau. We investigated the prevalence of a CSF AD profile in patients with SCI, naMCI, or aMCI and the association of this profile with cognitive outcome in each group. METHODS: Patients with SCI, naMCI, aMCI, and neurologically healthy controls were recruited from 20 memory clinics across Europe, between January, 2003, and June, 2005, into this prospective cohort study. A CSF AD profile was defined as an abnormal ratio of Abeta(42):tau. Patients were assessed annually up to 3 years. Outcome measures were changes in memory, overall cognition, mini-mental state examination (MMSE) score, daily function, and progression to AD-type dementia. FINDINGS: The CSF AD profile was more common in patients with SCI (31 of 60 [52%]), naMCI (25 of 37 [68%]), and aMCI (56 of 71 [79%]) than in healthy controls (28 of 89 [31%]). The profile was associated with cognitive decline in patients with naMCI (memory, MMSE, and daily function) and in patients with aMCI (MMSE and daily function). In patients with aMCI, a CSF AD profile was predictive of AD-type dementia (OR 26.8, 95% CI 1.6-456.4). INTERPRETATION: AD is a common cause of SCI, naMCI, and aMCI and is associated with cognitive decline in patients with naMCI or aMCI. Patients with SCI might be in the early stages of AD, and cognitive decline might become apparent only after longer follow-up. FUNDING: European Commission; Ana Aslan International Foundation.
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| 7. |
- Wallin, Anders, 1950, et al.
(författare)
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CSF biomarkers for Alzheimer's Disease: levels of beta-amyloid, tau, phosphorylated tau relate to clinical symptoms and survival
- 2006
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Ingår i: Dement Geriatr Cogn Disord. - : S. Karger AG. ; 21:3, s. 131-138
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) samples from 21 patients with a clinical diagnosis of Alzheimer's disease (AD) participating in a 5-year treatment study with the choline esterase inhibitor tacrin were retrospectively analyzed for the contents of beta-amyloid (Abeta42), total tau (T-tau) and phosphorylated tau (P-tau). A significant positive correlation between the level of P-tau and the number of symptoms according to the DSM-IV criteria (p = 0.041) and the NINCDS-ADRDA (p = 0.029) was observed (i.e. higher levels were found in cases with more symptoms). A significant positive correlation between T-tau, P-tau and ADAS-cog score was identified (i.e. higher levels were found with more severe cognitive dysfunction). Patients who died during the 5-year follow-up had significantly lower levels of Abeta42 (p = 0.011) than those who were still alive. Patients who had died in a 6-year follow-up had significantly lower levels of Abeta42 (p = 0.034) and higher levels of T-tau (p = 0.041) than patients still alive. CONCLUSION: CSF biomarkers do aid the clinical diagnosis of AD. Increased levels of P-tau and T-tau are possible markers for severity and abundance of symptoms in AD. Low levels of Abeta42 may indicate a higher risk of early death in AD.
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| 8. |
- Wallin, Anders, 1950, et al.
(författare)
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Donepezil in Alzheimer's disease : What to expect after 3 years of treatment in a routine clinical setting
- 2007
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Ingår i: Dementia and Geriatric Cognitive Disorders. - Basel : S. Karger AG. - 1420-8008 .- 1421-9824. ; 23:3, s. 150-160
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Clinical short-term trails have shown positive effects of donepezil treatment in patients with Alzheimer's disease. The outcome of continuous long-term treatment in the routine clinical settings remains to be investigated. Methods: The Swedish Alzheimer Treatment Study (SATS) is a descriptive, prospective, longitudinal, multicentre study. Four hundred and thirty-five outpatients with the clinical diagnosis of Alzheimer's disease, received treatment with donepezil. Patients were assessed with Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), global rating (CIBIC) and Instrumental Activities of Daily Living (IADL) at baseline and every 6 months for a total period of 3 years. Results: The mean MMSE change from baseline was positive for more than 6 months and in subgroups of patients for 12 months. After 3 years of treatment the mean change from baseline in MMSE-score was 3.8 points (95% CI, 3.0-4.7) and the ADAS-cog rise was 8.2 points (95% CI, 6.4-10.1). This is better than expected in untreated historical cohorts, and better than the ADAS-cog rise calculated by the Stern equation (15.6 points, 95% CI, 14.5-16.6). After 3 years with 38% of the patients remaining, 30% of the them were unchanged or improved in the global assessment. Conclusion: Three-year donepezil treatment showed a positive global and cognitive outcome in the routine clinical setting. Copyright © 2007 S. Karger AG.
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| 9. |
- Wallin, Åsa, et al.
(författare)
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Alzheimer's disease - Safety and dropout in long-term galantamine treatment in a routine clinical setting
- 2007
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Ingår i: New Trends in Alzheimer and Parkinson Related Disorders: ADPD 2007. ; , s. 245-249
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- 276 patients with Alzheimer's disease receiving galantamine in the Swedish Alzheimer Treatment Study were investigated for safety and dropout. Completion rates and reasons for dropout were monitored. The occurrence and time of death was investigated. Galantamine was well tolerated and few side effects were observed. The most frequent cause of dropout during the first year was side effects (n=9), the second and third year, because of adding memantine, which was overall the most frequent cause for dropout (28%). The observed death rate in the study population was not higher than in the average Swedish population (matched for age and gender). Completion-rates were high (51%) compared to previous 3-year studies of cholinesterase inhibitor treated patients.
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| 10. |
- Wallin, Åsa, et al.
(författare)
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Alzheimer’s disease with normal CSF biomarkers.
- 2012
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background/objectives: Alzheimer’s disease (AD) is currently diagnosed clinically using defined symptomatic diagnostic criteria. Pathological levels of CSF-biomarkers, high T-tau, P-tau and low Ab42 have been associated with AD however definition of cut off values differ. New diagnostic criteria that include the pathological CSF biomarkers have been suggested. How many AD patients in a routine clinical population have normal levels of the CSF biomarkers as defined by clinically defined cut-offs? Methods: Out-patients (n=151) with the clinical diagnosis of dementia as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th ed (DSM-IV) and probable or possible AD, according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and related Disorders Association (NINCDS-ADRDA, 1984), were included in this study. The number of symptoms according to these criteria and the levels of the CSF biomarkers Aβ42, T-tau and P-tau were evaluated at baseline. The patients received cholinesterase inhibitor (ChEI) treatment and were assessed with cognitive tests (MMSE, ADAS-cog) longitudinally for up to three years. Short-term ChEI-response was measured as cognitive change after 2 and 6 months of treatment. Long-term outcome was expressed as MMSE and ADAS-cog change per month. Pathological levels of CSF biomarkers were defined as in clinical routine; T-tau > 450 ng/l, P-tau > 60 ng/l and aβ42 < 400 ng/l. Results: In 15 % of the patients all three CSF biomarkers were normal. At baseline these patients had fewer symptoms (NINCDS-ADRDA), higher MMSE score, but then displayed the same rate of longitudinal cognitive decline as patients with pathological biomarkers. Furthermore, patients with normal CSF biomarkers did not differ in age of onset, duration of disease, IADL or ADAS-cog at baseline, completion rate or short-term response to treatment compared to those with pathological CSF biomarkers. Conclusion: Alzheimer’s disease with normal CSF displays the same cognitive short-term response to ChEI-treatment and clinical long-term outcome as patients with pathological CSF. These findings must be considered when defining future diagnostic criteria for AD.
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